ArticleFrontiers in cellular neuroscience2016
Neuronal Release of Cytokine IL-3 Triggered by Mechanosensitive Autostimulation of the P2X7 Receptor Is Neuroprotective.
Article in Frontiers in cellular neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 57 citations in OpenAlex.
- The P2X7 Receptor Regulates IL-1β Secretion in the Human Retina.International journal of molecular sciences · 2025Article
- Therapeutic potential of P2X7 receptor in retinal diseases.Purinergic signalling · 2025Review
- Neurons as Immunomodulators: From Rapid Neural Activity to Prolonged Regulation of Cytokines and Microglia.Annual review of biomedical engineering · 2025Review
- Priming and release of cytokine IL-1β in microglial cells from the retina.Experimental eye research · 2025Article
- Fluorescent identification of axons, dendrites and soma of neuronal retinal ganglion cells with a genetic marker as a tool for facilitating the study of neurodegeneration.FASEB bioAdvances · 2025Article
- Targeting the P2X7 receptor in cerebrovascular diseases: from molecular mechanisms to preclinical therapeutic potential.Frontiers in pharmacology · 2025Review
- Increased Pan-Type, A1-Type, and A2-Type Astrocyte Activation and Upstream Inflammatory Markers Are Induced by the P2X7 Receptor.International journal of molecular sciences · 2024Article
- Interleukin 3 Inhibits Glutamate-Cytotoxicity in Neuroblastoma Cell Line.Neurochemical research · 2024Article
- Interactions between Cytokines and the Pathogenesis of Prion Diseases: Insights and Implications.Brain sciences · 2024Review
- Article
- Interleukin-3 gets a fresh start in the brain.Genes and immunity · 2023Article
- 3D bioengineered neural tissue generated from patient-derived iPSCs mimics time-dependent phenotypes and transcriptional features of Alzheimer's disease.Molecular psychiatry · 2023Article
- Long-term Effects of the pituitary-adenylate cyclase-activating Polypeptide (PACAP38) in the Adult Mouse Retina: Microglial Activation and Induction of Neural Proliferation.Neurochemical research · 2023Article
- The Mechanosensitive Piezo1 Channel Mediates Mechanochemical Transmission in Myopic Eyes.Investigative ophthalmology & visual science · 2023Article
- NLRP3 Inflammasome's Activation in Acute and Chronic Brain Diseases-An Update on Pathogenetic Mechanisms and Therapeutic Perspectives with Respect to Other Inflammasomes.Biomedicines · 2023Review
- Bidirectional crosstalk between the peripheral nervous system and lymphoid tissues/organs.Frontiers in immunology · 2023Review
- Mitochondria-associated endoplasmic reticulum membranes (MAMs) and their role in glaucomatous retinal ganglion cell degeneration-a mini review.Frontiers in neuroscience · 2023Review
- Article
- Importance of crosstalk between the microbiota and the neuroimmune system for tissue homeostasis.Clinical & translational immunology · 2022Review
- Rapid morphologic changes to microglial cells and upregulation of mixed microglial activation state markers induced by P2X7 receptor stimulation and increased intraocular pressure.Journal of neuroinflammation · 2021Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Mechanical strain due to increased pressure or swelling activates inflammatory responses in many neural systems. As cytokines and chemokine messengers lead to both pro-inflammatory and neuroprotective actions, understanding the signaling patterns triggered by mechanical stress may help improve overall outcomes. While cytokine signaling in neural systems is often associated with glial cells like astrocytes and microglia, the contribution of neurons themselves to the cytokine response is underappreciated and has bearing on any balanced response. Mechanical stretch of isolated neurons was previously shown to trigger ATP release through pannexin hemichannels and autostimulation of P2X7 receptors (P2X7Rs) on the neural membrane. Given that P2X7Rs are linked to cytokine activation in other cells, this study investigates the link between neuronal stretch and cytokine release through a P2X7-dependent pathway. Cytokine assays showed application of a 4% strain to isolated rat retinal ganglion cells (RGCs) released multiple cytokines. The P2X7R agonist BzATP also released multiple cytokines; Interleukin 3 (IL-3), TNF-α, CXCL9, VEGF, L-selectin, IL-4, GM-CSF, IL-10, IL-1Rα, MIP and CCL20 were released by both stimuli, with the release of IL-3 greatest with either stimuli. Stretch-dependent IL-3 release was confirmed with ELISA and blocked by P2X7R antagonists A438079 and Brilliant Blue G (BBG), implicating autostimulation of the P2X7R in stretch-dependent IL-3 release. Neuronal IL-3 release triggered by BzATP required extracellular calcium. The IL-3Rα receptor was expressed on RGCs but not astrocytes, and both IL-3Rα and IL-3 itself were predominantly expressed in the retinal ganglion cell layer of adult retinal sections, implying autostimulation of receptors by released IL-3. While the number of surviving ganglion cells decreased with time in culture, the addition of IL-3 protected against this loss of neurons. Expression of mRNA for
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.